Mechanism of antidepressant action of kaji-ichigoside F1 based on metabolomics.
10.19540/j.cnki.cjcmm.20250331.401
- Author:
Mao-Yang HUANG
1
;
Fa-Ju CHEN
1
;
Lang ZHOU
1
;
Qi-Ji LI
1
;
Xiao-Sheng YANG
1
Author Information
1. State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine,Guizhou Medical University Guiyang 561113, China Natural Products Research Center of Guizhou Province Guiyang 550014, China.
- Publication Type:Journal Article
- Keywords:
depression;
kaji-ichigoside F1;
mechanism of action;
metabolomics
- MeSH:
Animals;
Mice;
Antidepressive Agents/administration & dosage*;
Metabolomics;
Depression/genetics*;
Male;
Drugs, Chinese Herbal/administration & dosage*;
Disease Models, Animal;
Hippocampus/metabolism*;
Behavior, Animal/drug effects*;
Humans
- From:
China Journal of Chinese Materia Medica
2025;50(16):4574-4583
- CountryChina
- Language:Chinese
-
Abstract:
In this study, serum metabolomics techniques and molecular biology methods were used to investigate the intervention effect of kaji-ichigoside F1 on chronic unpredictable mild stress(CUMS) depression mouse model and its mechanism. The CUMS depression mouse model was constructed, and the mice were divided into blank group, model group, escitalopram(ESC, 10 mg·kg~(-1)) group, and low-dose, medium-dose, and high-dose kaji-ichigoside F1 groups(1, 2, and 4 mg·kg~(-1)). CUMS modeling was performed on all mice except the blank group, and the cycle was four weeks. At the end of modelling, ESC and kaji-ichigoside F1 were administered by gavage once a day for 28 days. After the end of the administration, behavioral testing(sucrose preference test, open field test, forced swimming test, and tail suspension test) was conducted to evaluate the improvement of depression symptoms of different doses of kaji-ichigoside F1 on CUMS depression mouse model. The morphology of neurons and the number of Nissl bodies in the hippocampus were observed by Nissl staining. Metabolomics technique was used to analyze the changes in serum differential metabolites in mice. Protein expression levels of P2X7 purinergic receptor(P2X7R), adenosine A1 receptor(A1R), and adenosine receptor A2A(A2AR) in mouse hippocampus were detected by Western blot. The results showed that compared with that in the blank group, the body weight of mice in the model group was significantly decreased, and the sucrose preference rate was significantly decreased. The immobility time was significantly increased in the forced swimming and tail suspension tests, and the total moving distance was significantly decreased in the open field test. The number of Nissl bodies was significantly decreased, and the depression-like behavior and the number of Nissl bodies in the hippocampus of mice were significantly improved after administration of kaji-ichigoside F1. In the metabonomics analysis, the purine metabolism of serum after kaji-ichigoside F1 administration was involved in the metabolic passage of depression, and Western blot analysis verified the expression of P2X7R, A1R, and A2AR proteins in purine metabolic pathways. The results show that kaji-ichigoside F1 significantly decreases the expression of P2X7R and A2AR proteins in the hippocampus of CUMS model mice and increases the expression level of A1R proteins. It is suggested that kaji-ichigoside F1 may play an antidepressant role by regulating the expression of P2X7R, A1R, and A2AR proteins in the purine metabolism pathway.
